Whole Exome Sequencing Study Suggests an Impact of FANCA, CDH1 and VEGFA Genes on Diffuse Gastric Cancer Development

Abstract

Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. Hereditary predisposition for GC is not fully elucidated so far. The aim of this study was identification of possible new candidate genes, associated with the increased risk of gastric cancer development. Whole exome sequencing (WES) was performed on 18 DNA samples from adenocarcinoma specimens and non-tumor-bearing healthy stomach tissue from the same patient. Three pathogenic variants were identified: c.1320+1G>A in the CDH1 gene and c.27_28insCCCAGCCCCAGCTACCA (p.Ala9fs) of the VEGFA gene were found only in the tumor tissue, whereas c.G1874C (p.Cys625Ser) in the FANCA gene was found in both the tumor and normal tissue. These changes were found only in patients with diffuse gastric cancer and were absent in the DNA of healthy donors.

Editorial for the Special Issue “Genetics and Genomics of Gastrointestinal Cancers: From Prevention to Treatment”

“…Whole Exome Sequencing is another approach for DNA analysis, useful in identifying genetic variants both at the germline and at the somatic level, and can represent a powerful tool to investigate hereditary predisposition to rare diseases. By using this technique, Nurgalieva and colleagues [ 10 ] analyzed genomic DNA from tumors and paired normal tissue samples in nine patients affected by gastric adenocarcinoma. They identified three pathogenic variants in two diffuse GC cases: a pathogenic variant in the CDH1 gene in one patient and two pathogenic variants in the VEGFA and FANCA genes in a second patient.…”